The research proposal is for study of the permanent effects of acute ischemia on myocardial metabolism and mechanical function. Ischemia will differentially affect metabolic pathways in the heart such that following restoration of coronary blood flow optimal rates of energy production are not possible. It is postulated that the rate of energy production may be the limiting factor for mechanical function in the post-ischemic heart. The studies will be directed towards further study of the rates of energy production from aerobic and non-aerobic pathways in normal and post-ischemic hearts. The rates of energy production and utilization under these conditions will be related to the mechanical function of the heart. In addition, studies will be undertaken to determine the rate-limiting steps within the energy producing pathways of post-ischemic hearts for comparison to non-ischemic hearts. The factors which are limiting the rate of energy production following ischemia will be studied and attempts will be made to increase the energy supply. The effectiveness of increased energy production on increasing the mechanical function of the post-ischemic heart will also be determined. These studies will give greater insight into factors which control basic energy metabolism in the heart and should lead to development of interventions which will protect ischemic myocardial cells and prolong the period of ischemia before irreversible damage occurs. BIBLIOGRAPHIC REFERENCES: Rovetto, M.J., W.F. Lamberton and J.R. Neely. Mechanisms of glycolytic inhibition in ischemic rat hearts. Circulation Research 37:742-751, 1975. Rovetto, M.J. Effect of hyaluronidase on glucose utilization and coronary flow in the ischemic rat heart. Fed. Proc. 35(3):350, 1976 (abstract).